Apparatus and methods of using built-in micro-spectroscopy micro-biosensors and specimen collection system for a wireless capsule in a biological body in vivo

Abstract

A wireless capsule as a disease diagnosis tool in vivo can be introduced into a biological body by a native and/or artificial open, or endoscope, or an injection. The information obtained from a micro-spectrometer, and/or an imaging system, or a micro-biosensor, all of which are built-in a wireless capsule, can be transmitted to the outside of the biological body for medical diagnoses. In addition, a real-time specimen collection device is integrated with the diagnostic system for the in-depth in vitro analysis

1 . A wireless capsule that used inside a biological body as a diagnosis tool in vivo comprises 
 a) Examining means for medical diagnosis;    b) Means for specimen collection;    c) Means for positions and trace;    d) A microprocessor for data storage, data analysis, data transmission and system control;    e) Means for communication to outside of the biological body;    f) A protect capsule.    
     
     
         2 . The wireless capsule claimed in  claim 1  wherein said the biological body in vivo is a living human or a living animal.  
     
     
         3 . The wireless capsule claimed in  claim 1  wherein the inside of a biological body is: 
 a. Gastrointestinal tract,    b. Biliary tract;    c. Pancreatic tract;    d. Breast ducts;    e. Urinary tract;    f. GYN tract;    g. Brain ventricular system;    h. Cardiovascular system.    
     
     
         4 . The wireless capsule claimed in  claim 1  wherein said examining means is a micro-spectrometer and/or a micro-biosensor with a microprocessor.  
     
     
         5 . The wireless capsule claimed in  claim 1  wherein said the micro-spectrometer claimed in  claim 4  comprises a light source for illumining an area inside biological body or a micro-biosensor, an optical sensor for detecting light from the irradiated area and other optical assistances at one or multiple wavelengths. The micro-spectrometer comprises a set of beam splitter/narrow band filter set as shown in FIG. 2  or an array-wavelength-grating to disperse different wavelengths into different detectors.  
     
     
         6 . The wireless capsule claimed in  claim 5  wherein said light source is a broad-spectrum light of light emitting diode (LED), laser diode, or flash lamp or tunable diode lasers with or without wavelength selection filters covering wavelength range from 190 nm to 2500 nm.  
     
     
         7 . The wireless capsule claimed in  claim 6  wherein said LED is 
 a. LED (spectral bandwidth <100 nm): the peak illumination wavelength spans from 280 nm to 2500 nm;    b. LED (spectral bandwidth >300 nm): the peak illumination wavelength spans from 280 nm to 2500 nm;    c. LED as a white light source (5900 K black body radiation) as the Mercury arc lamp;    d. Laser diode whose peak emission wavelength spans from 250 nm to 2500 nm;    e. Combination of several LEDs or laser diodes using a hologram to form a wideband light source with a controlled spectral intensity distribution;    f. Combined NIR LEDs or laser diodes with white light sources using holograms to perform white light source;    g. Combined UV LEDs (wavelength from 190 nm to 350 nm) with white light source.    
     
     
         8 . The wireless capsule claimed in  claim 5  wherein said the optical sensor is configured with a variety of image and/or different fluorescence and/or absorption and/or diffuse reflect and/or transmission spectra, which have one or differing excitation wavelengths to detect chemical and biological threats, or as an optical transducer for biosensors, or as an indicator for specimen collection in vivo.  
     
     
         9 . The wireless capsule claimed in  claim 5  wherein said the optical sensor comprises one of: 
 a. One or multiple photodiodes;    b. One or multiple photomultipliers;    c. A CCD chip with pixel size: 10×10 to 4000×4000, spectral spanned from 190 nm to 2500 nm;    d. A CCD chip shared by five independent sets of imaging optics, including one wide-angle front imaging and four side high resolution imaging mechanics;    e. A CMOS imaging chip: pixel size: 10×10 to 4000×4000, spectral spanned from 190 nm to 1100 nm;    f. A NIR camera: pixel size: 10×10 to 2000×2000, spectral sensitivity from 800 nm to 2500 nm;    g. One or multiple PIN diodes with spectral range from 190 nm to 2500 nm;    h. One or multiple avalanched photodiodes (APD) with spectral range from 190 nm to 2500 nm;    i. A diode array with the total number of diodes from 10 to 8000 and the spectral range from 190 nm to 2500 mn.    
     
     
         10 . The wireless capsule claimed in  claim 5  wherein said the other optical assistance is: 
 a. Lenses: Collimation of the illumination light source to illuminate the object, collection of the back-scattered light from the object and image to the optical detector, collection of the transmission light from the object and image to the optical detector, collection of the fluorescence light from the object and image to the optical detector;    b. Color filters: Narrowband filters with the center wavelength spanned from 190 nm to 2500 nm, broadband filters with the center wavelength spanned from 190 nm to 2500 nm;    c. Polarization filters covering the wavelength range from 190 nm to 2500 nm;    d. Spectral reformer: adjust the intensity spectral distribution of the illumination to match white light spectrum, mercury arc spectrum, sun light spectrum;    e. Beam splitters: high throughput efficiency for the illumination light transmission and the signal light reflection based on the geometrical factor and wavelength;    f. Tunable narrow band filters: by rotating the hologram, the change of the effective grating space as a re-configurable narrow band color filter for signal collection.    
     
     
         11 . The wireless capsule claimed in  claim 10  wherein said the lens is: 
 a. A single lens;    b. A combination of four sets of Front-lens Side-lens Mirror Rear-lens structure (The side view and cross-section view is shown in  FIG. 9 , and 3D drawing is shown in  FIGS. 10A and 10B ), where the CCD chip amounted in two different ways;    c. A combination of four sets of Front-lens Mirror Side-lens structure. (The side view and cross-section view is shown in  FIG. 11 , and 3D drawing is shown in  FIGS. 12A and 12B  with different ways to mount CCD chip);    d. A combination of front lens and the spatial surface profile of front part of optical shell widens range of imaging angle.    
     
     
         12 . The wireless capsule claimed in  claim 1  wherein said the optical transducer for biosensor is a micro-spectrometer, described in  claim 5 , with a microprocessor.  
     
     
         13 . The wireless capsule claimed in  claim 4  wherein said the biosensor is one of: 
 a. A DNA chip;    b. An enzyme chip;    c. An antibody chip;    d. A cell or cellular system chip;    e. A bio-mimetic chip;    f. A set of micro-sphere sensors;    g. A micro-array smart pin sensor.    
     
     
         14 . The wireless capsule claimed in  claim 1  wherein said the biosensor has one or multiple sets in the wireless capsule for different area detection.  
     
     
         15 . The wireless capsule claimed in  claim 1  wherein said the biosensor: 
 a. Without a transducer;    b. With an optical transducer;    c. With an electrochemical transducer; or    d. With a Mass-based transducer.    
     
     
         16 . The wireless capsule as claimed in  claim 1  wherein said the means for specimen collection is controlled by examining means, described in  claim 4 , with a microprocessor.  
     
     
         17 . The wireless capsule as claimed in  claim 1  wherein said the specimen is liquid or solid samples. 
 Specimen collection means for solid samples are:    a. A cup-type device with sharp diamond blade or chain saw at the rim;    b. A hollow drill.    Specimen collection means for liquid samples are:    a. Needles;    b. Hollow fibers;    c. Reverse osmosis;    d. Permeation;    e. Porous structure.    
     
     
         18 . The wireless capsule as claimed in  claim 1  wherein said the protect capsule has a length from 1 mm up to 30 mm and has any form. The protect capsule is made of plastic, Teflon, silicon and/or metal.  
     
     
         19 . The wireless capsule as claimed in  claim 1  wherein said the communication means is a system of emitting electromagnetic waves, using radio frequency (RF). The position and trace information of a said capsule to a receiver outside of the biological body is using electromagnetic fields and waves from: 
 a. RF;    b. Magnet;    c. Radio-Isotope.    
     
     
         20 . The wireless capsule as claimed in  claim 1  wherein said the microprocessor is: 
 a. Micro-spectrometer system;    b. VLSI circuit;    c. Si CMOS circuit;    d. Any semiconductor chip.    
     
     
         21 . A system for diagnosis in internally a biological body with wireless capsule, said the system comprises: 
 a. Means for receiving wireless signals;    b. A computer with software for analyzing wireless signals; and    c. Wireless capsule as claimed in  claim 1 .    
     
     
         22 . A method of diagnoses diseases comprises the steps of: 
 a. Providing the wireless capsule claimed in  claim 1;     b. Providing a photosensitized dye and/or other drug or not;    c. Introducing the wireless capsule into the biological body;    d. Collecting examination information through the microprocessor via micro-spectroscopy and/or micro-biosensor;    e. Transmitting the examination information to a receiver located outside a biological body; or    f. Collecting specimen indicated by the exanimation information obtained.    
     
     
         23 . The method as claimed in  claim 22  wherein said introducing the wireless capsule into the biological body is via: 
 a. A native open;    b. An artificial open;    c. An endoscope;    d. An injection.    
     
     
         24 . The method as claimed in  claim 22  wherein diagnosing diseases through the wireless capsule inside of a biological body in vivo is: 
 a. Spectroscopy;    b. Imaging;    c. Biosensor with or without a transducer;    d. Collecting the specimen for further outside analysis.    
     
     
         25 . The method as claimed in  claim 22  wherein said examining information is: 
 a. Day light imaging of tissue and/or juice;    b. Scatter spectra and/or imaging of tissue and/or juice;    c. Absorption spectra and/or imaging of tissue and/or juice;    d. Transmission spectra and/or imaging of tissue and/or juice;    e. Fluorescence spectra and/or imaging of tissue and/or juice;    f. Raman spectra and/or imaging of tissue and/or juice;    g. Differ and reflectance spectra and/or imaging of tissue and/or juice;    h. Time-resolved spectra and/or imaging of tissue and/or juice;    i. DNA analyses of tissue and/or juice;    j. RNA analyses of tissue and/or juice;    k. Protein analyses of tissue and/or juice;    l. Antibody analyses of tissue and/or juice;    m. Enzyme analyses of tissue and/or juice;    n. Cell and/or cellular system analyses of tissue and/or juice;    o. pH analysis of tissue and/or juice;    p. Osmolarity analysis of tissue and/or juice;    q. Temperature analysis of tissue and/or juice;    r. Ion concentration analyses of tissue and/or juice;    s. SaO 2  analysis of tissue and/or juice;    t. SaCO 2  o analysis f tissue and/or juice;    u. Hemoglobin analysis of tissue and/or juice;    v. Glucose analysis of tissue and/or juice;    w. Cholesterol analysis of tissue and/or juice;    x. Cholesterol esters analysis of tissue and/or juice;    y. Lipoproteins analysis of tissue and/or juice;    z. Triglyceride analysis of tissue and/or juice;    aa. Any other physiological parameter analysis of tissue and/or juice.    
     
     
         26 . The method as claimed in  claim 22  wherein said a photosensitized dye is: 
 a. ICG;    b. Pure hematoporphyrin Hp/5;    c. HEMATODREX (Bulgarian hematoporphyrin derivative);    d. Photofrin;    e. Pure hematoporphyrin;    f. Hematoporphyrin derivative (HpD);    g. Hematoporphyrin;    h. Phototoxic drug;    i. Porfimer sodium;    j. Meso-tetrahydroxyphenyl chlorine;    k. 5-aminolevulinic acid (ALA)-induced protoporphyrin IX, ALA thermosetting gel Pluronic F-127;    l. 5-aminolevulinic acid esters on protoporphyrin IX;    m. 5-aminolevulinic acid;    n. 5-aminolevulinic acid-induced protoporphyrin IX;    o. Meso-tetrahydroxyphenylchlorin;    p. Pyropheophorbide-alpha-hexyl-ether (HPPH-23);    q. Di-sulphonated aluminium phthalocyanine (A1S2Pc).    
     
     
         27 . The method as claimed in  claim 26  wherein said providing a photosensitized dyes is: 
 a. Swallow;    b. Injection;    c. Local provided.    
     
     
         28 . The method as claimed in  claim 24  wherein said using spectroscopy is using spectral analysis of: 
 a. Scattering: Given an illumination source of I in (λ 1 ) with known intensity and wavelength, the output I out (λ 1 ) has the same wavelength using the function of amplitude, angular distribute, and/or polarization information to determine diseases;    b. Absorption: Using N illumination sources of I in (λ 1 ), I in (λ 2 ), . . . I in (λ N ) with known intensity, the measured intensity change from the output I out (λ 1 ), I out (λ 2 ), . . . I out (λ N ) will be collected and normalized with I in  to determine diseases. N is an integer number greater or equal 2;    c. Fluorescence: Given an illumination source of I in (λ 1 ) with known intensity and wavelength, I in (λ 1 ) the output intensities at different wavelengths, I out (λ F     1   ,), . . . I out (λ F     N   ) will be measured and analyzed to determine diseases;    d. Excitation: Using N illumination sources of I in (λ 1 ), I in (λ 2 ), . . . I in (λ N ) with known intensity, I in , and wavelength, λ i , then measure the output intensities emission at a particular wavelength (I out (λ p ),) illuminated from various input wavelength (λ i ) to determine diseases. i is an integer number from 1 to N;    e. Raman: Using one illumination source of I in (λ 1 ) with known intensity and wavelength, the output signals at various phonon vibration wavelengths (λ R     i   ) will be measured to determine the chemical compositions of each molecular chain. λ R     i    is the i-th Raman signal wavelength and i is an integer number from 1 to N. The larger the N is, the more accurate disease information will be obtained;    f. Nonlinear: Using one illumination source of I in (λ 1 ) with known intensity and wavelength, the output signals at various high order harmonic generation wavelengths (λ R/i ) will be measured to reveal tissue structural behaviors. i is an integer number from 1 to N. For example, the wavelength of the second harmonic generation is λ/2, and the third harmonic generation is λ/3, and the n-th harmonic generation is λ/N;    g. Time-resolved: Using a pulsed illumination source of I in (λ 1 , t), the output signal intensity at a particular wavelength, λ F , will be measured as a function of time: t 1 , . . . , t N ;    h. Beam Forming Optics: using both diffuser and hologram: holographic Optical Elements as multi-function lenses, color filters, spectral reformer, beam splitter for illumination light focusing, signal light collection, and wavelength spectral correction;    i. Apply provided photosensitized dyes for different spectral analyses.    
     
     
         29 . The method as claimed in  claim 24  wherein said imaging is: 
 a. Day light imaging;    b. Fluorescence imaging;    c. Absorption imaging;    d. Scatter imaging;    e. Time-resolved imaging;    f. Hologram;    g. Thermal imaging;    h. Pseudo color imaging.    
     
     
         30 . The method as claimed in  claim 22  wherein said using biosensor with or without an optical transducer is: 
 a. Hepatocarcinoma-intestine-pancreas/pancreatitis-associated-protein I (HIP/PAP-I) in pancreatic juice for early diagnosis of pancreatic adenocarcinoma;    b. Human express sequence tags (ESTs) for lung and prostate cancers;    c. Single-nucleotide polymorphism (SNP) for cancer, diabetes, vascular disease and some forms of mental illness;    d. Loss of heterozygosity (LOH) for human tumors;    e. Human genes BRCA1 and BRCA 2, p53, p450 for cancers;    f. Comparative genomic hybridization (CGH) data for ovarian, prostate, breast, urinary bladder caner and renal cell carcinoma;    g. The dyed antibody of p53 tumor suppressor gene in the GI wall for cancer diagnoses;    h. Any dye-marked target that has an optical characteristic.    
     
     
         31 . The method as claimed in  claim 28  wherein said the method of collecting specimen can be controlled by: 
 a. An indication from examination means inside of wireless capsule;    b. An program from microprocessor inside of wireless capsule;    c. An order from the outside of biological body.    
     
     
         32 . The method as claimed in  claim 24  wherein said the method of collecting specimen is: 
 a. Rotation monitoring and control by motorized driving inner core to move inside outside shell rack;    b. Direction monitoring and control with the force interaction between built-in magnet bar and external magnetic field;    c. Sampling and monitoring by two motorized driving blades to open and close;    d. Two samples can be collected with one for each side;    e. Sample storage for each collection;    f. Two blades closing makes a sealing storage space;    g. Pin-hole imager monitors specimen collection.